New specific marker of cytochrome P450 1A2 activity.

Various methods were proposed for phenotyping of patients by activity of cytochrome P450 1A2, each has some advantages and disadvantages. However, no reference parameters were developed for measuring CYP1A2 activity that could be used as a unified standard for phenotyping of patients. We propose a mathematic model of caffeine metabolism allowing calculation of rate constants for the formation of its primary metabolites.

[On the possibility of patient phenotyping on the basis of cytochrome p-450 1A2 isoenzyme activity using caffeine as the test substrate].

Reactions of caffeine biotransformation and enzymes participating in the caffeine metabolism via the paraxanthine pathway are reviewed. Data on the drugs metabolized mainly in cytochrome P-450 1A2 isoenzyme (CYP 1A2) are analyzed. Information on the phenotypes of CYP 1A2 activity in smoking healthy volunteers, women using oral contraceptives, diabetes patients, those with liver disorders, etc.

[Chromatographic determination of caffeine and its metabolites in saliva and plasma].

The authors made a comparative analysis of the well-known high performance liquid chromatographic (HPLC) techniques to detect caffeine and its primary metabolites in saliva and plasma when during their oral administration. The studies yielded a new specific and sensitive procedure for HPLC analysis of caffeine and its major metabolites, whose distinctive feature was to simultaneously separate six substances with a possibility of determining the activity of the cytochrome P-450 isozymes 1A2, 2E1, and 3A4.